Hydroxyethylene dipeptide mimics are commonly employed as isosteric replacements for a dipeptide moiety in peptidyl enzyme inhibitors. For example, the substrate for renin contains a Leu-Val dipeptide moiety which is cleaved to produce angiotensin I, the precursor to the hypertensive peptide angiotensin II. A number of inhibitors of renin have been reported which incorporate a noncleavable mimic of the Leu-Val dipeptide having the formula 1. ##STR3##
An intermediate that is commonly used to prepare compounds incorporating 1 (R.sub.1 is loweralkyl, cycloalkyl, cycloalkylalkyl, phenyl or benzyl, R.sub.2a is hydrogen or loweralkyl and R.sub.2b is hydrogen, loweralkyl, cycloalkyl or phenyl) is the compound of formula 2. See Shiozak, et al., Tet. Lett. 30 3669 (1989); Nishi, et al., Chem. Lett. 1993 (1989); Bradbury, et al., Tet. Lett. 30 3845 (1989); Chakravarty, et al., Tet. Lett. 30 415 (1989); Herold, et al, J. Org. Chem. 54 1178 (1989); Pals, et al., European Patent Application No. EP173481, published Mar. 5, 1986; and Wuts, PCT Patent Application No. WO90/00166, published Jan. 11, 1990. ##STR4##
The reported syntheses of 2 are limited in their ability to readily provide stereochemically pure products with a minimum amount of purifications and isomeric separations. Thus, there is a continuing need to develop more effective syntheses of 2 (R.sub.1 is loweralkyl, cycloalkyl, cycloalkylalkyl, phenyl or benzyl, R.sub.2a is hydrogen or loweralkyl and R.sub.2b is hydrogen, loweralkyl, cycloalkyl or phenyl).